tbuckley/cabot-search huggingface dataset:
Orismilast in moderate-to-severe psoriasis: Efficacy and safety from a 16-week, randomized, double-blinded, placebo-controlled, dose-finding, and phase 2b trial (IASOS)
Authors: Richard B. Warren, Lars E. French, Andrew Blauvelt, Richard G. Langley, Alexander Egeberg, Ulrich Mrowietz, Hamish J.A. Hunter, Melinda Gooderham, Per Soerensen, Philippe Andres, Morten O.A. Sommer, Anna Carlsson, Kim D. Kjøller, Bruce E. Strober
Journal: Journal of the American Academy of Dermatology (2023)

Background Orismilast is a novel oral phosphodiesterase 4 (PDE4) B/D inhibitor being investigated as a potential treatment for moderate-to-severe psoriasis. Objective To evaluate efficacy and safety of orismilast modified-release formulation in moderate-to-severe psoriasis. Methods This multicenter, randomized (1:1:1:1 to 20, 30, 40 mg orismilast or placebo, twice daily), double-blinded, placebo-controlled, parallel-group, phase 2b, 16-week, dose-ranging study evaluated orismilast in adults with moderate-to-severe plaque psoriasis (NCT05190419). Efficacy endpoints were analyzed using multiple imputation. Results Of 202 randomized patients, baseline characteristics were balanced across arms, except greater severe disease proportions for orismilast versus placebo. Orismilast showed significant improvements in the primary endpoint, percentage change in Psoriasis Area and Severity Index (PASI), from baseline to week 16 (orismilast –52.6% to –63.7%; placebo, –17.3%; all P<0.001). Greater proportions receiving orismilast achieved PASI75 (39.5% to 49.0%; P<0.05) and PASI90 (22.0% to 28.3%; P<0.05 for 20 and 40 mg) versus placebo (PASI75, 16.5%; PASI90, 8.3%) at week 16. Safety findings were as expected with PDE4 inhibition; dose-dependent tolerability effects observed. Limitations Small sample size, disease severity imbalance between groups, limited duration and diversity in study population. Conclusion Orismilast demonstrated greater efficacy versus placebo and a safety profile in line with PDE4 inhibition.
Letter 2 regarding “Assessing the performance of ChatGPT in answering questions regarding cirrhosis and hepatocellular carcinoma”
Authors: Yiwen Zhang, Liwei Wu, Zepeng Mu, Linlin Ren, Ying Chen, Hanyun Liu, Lili Xu, Yangang Wang, Yaxing Wang, Susan Cheng, Yih Chung Tham, Bin Sheng, Tien Yin Wong, Hongwei Ji
Journal: Clinical and Molecular Hepatology (2023)
Brentuximab vedotin with dacarbazine or nivolumab as frontline cHL therapy for older patients ineligible for chemotherapy
Authors: Jonathan W. Friedberg, Rodolfo Bordoni, Dipti Patel-Donnelly, Timothy Larson, Jerome Goldschmidt, Ralph Boccia, Vivian J. M. Cline, Adrija Mamidipalli, Jingmin Liu, Alev Akyol, Christopher A. Yasenchak
Journal: Blood (2023)
A prospective multi-institutional study of eculizumab to treat high-risk stem cell transplantation–associated TMA
Authors: Sonata Jodele, Christopher E. Dandoy, Paibel Aguayo-Hiraldo, Adam Lane, Ashley Teusink-Cross, Anthony Sabulski, Kana Mizuno, Benjamin L. Laskin, Jason Freedman, Stella M. Davies
Journal: Blood (2023)
Entirely noninvasive outcome prediction in central nervous system lymphomas using circulating tumor DNA
Authors: Jan-Michel Heger, Julia Mattlener, Jessica Schneider, Philipp Gödel, Noëlle Sieg, Fabian Ullrich, Richard Lewis, Teodora Bucaciuc-Mracica, Roland F. Schwarz, Daniel Rueß, Maximilian I. Ruge, Manuel Montesinos-Rongen, Martina Deckert, Tobias Blau, Nadine Kutsch, Hyatt Balke-Want, Jonathan Weiss, Kerstin Becker, H. Christian Reinhardt, Michael Hallek, Peter Borchmann, Bastian von Tresckow, Sven Borchmann
Journal: Blood (2023)
Discovery of a potent and highly selective inhibitor of SIRT6 against pancreatic cancer metastasis in vivo
Authors: Xinyuan Xu, Qian Zhang, Xufeng Wang, Jing Jin, Chengwei Wu, Li Feng, Xiuyan Yang, Mingzhu Zhao, Yingyi Chen, Shaoyong Lu, Zhen Zheng, Xiaobing Lan, Yi Wang, Yan Zheng, Xuefeng Lu, Qiufen Zhang, Jian Zhang
Journal: Acta Pharmaceutica Sinica B (2023)

Pancreatic cancer, one of the most aggressive malignancies, has no effective treatment due to the lack of targets and drugs related to tumour metastasis. SIRT6 can promote the migration of pancreatic cancer and could be a potential target for antimetastasis of pancreatic cancer. However, highly selective and potency SIRT6 inhibitor that can be used
Reply to Greg Shaw, John D. Kelly, and Monique J. Roobol’s Letter to the Editor re: Freddie C. Hamdy, Jenny L. Donovan, J. Athene Lane, et al. Fifteen-Year Outcomes After Monitoring, Surgery, or Radiotherapy for Prostate Cancer. N Engl J Med 2023;388:1547–58
Authors: Freddie C. Hamdy, Jenny L. Donovan
Journal: European Urology (2023)
Effect of an artificial intelligence-assisted system on endoscopic diagnosis of superficial oesophageal squamous cell carcinoma and precancerous lesions: a multicentre, tandem, double-blind, randomised controlled trial
Authors: Xiang-Lei Yuan, Wei Liu, Yi-Xiu Lin, Qian-Yi Deng, Yuan-Ping Gao, Ling Wan, Bin Zhang, Tao Zhang, Wan-Hong Zhang, Xiao-Gang Bi, Guo-Dong Yang, Bi-Hui Zhu, Fan Zhang, Xiao-Bo Qin, Feng Pan, Xian-Hui Zeng, Hunza Chaudhry, Mao-Yin Pang, Juliana Yang, Jing-Yu Zhang, Bing Hu
Journal: The Lancet. Gastroenterology & hepatology (2023)
Concomitant 1q+ and t(4;14) influences disease characteristics, immune system, and prognosis in double-hit multiple myeloma
Authors: Michael Ozga, Qiuhong Zhao, Laila Huric, Cecelia Miller, Ashley Rosko, Abdullah Khan, Elvira Umyarova, Don Benson, Francesca Cottini
Journal: Blood Cancer Journal (2023)
A novel transgenic mouse line with hippocampus-dominant and inducible expression of truncated human tau
Authors: Yang Gao, Yuying Wang, Huiyang Lei, Zhendong Xu, Shihong Li, Haitao Yu, Jiazhao Xie, Zhentao Zhang, Gongping Liu, Yao Zhang, Jie Zheng, Jian-Zhi Wang
Journal: Translational Neurodegeneration (2023)

Intraneuronal accumulation of hyperphosphorylated tau is a defining hallmark of Alzheimer's disease (AD). However, mouse models imitating AD-exclusive neuronal tau pathologies are lacking.
Biomarkers of immediate drug hypersensitivity
Authors: Cristobalina Mayorga, Adriana Ariza, Rosa Muñoz‐Cano, Vito Sabato, Inmaculada Doña, Maria J. Torres
Journal: Allergy (2023)

Abstract Immediate drug hypersensitivity reactions (IDHRs) are a burden for patients and the health systems. This problem increases when taking into account that only a small proportion of patients initially labelled as allergic are finally confirmed after an allergological workup. The diverse nature of drugs involved will imply different interactions with the immunological system. Therefore, IDHRs can be produced by a wide array of mechanisms mediated by the drug interaction with specific antibodies or directly on effector target cells. These heterogeneous mechanisms imply an enhanced complexity for an accurate diagnosis and the identification of the phenotype and endotype at early stages of the reaction is of vital importance. Currently, several endophenotypic categories (type I IgE/non‐IgE, cytokine release, Mast‐related G‐protein coupled receptor X2 (MRGPRX2) or Cyclooxygenase‐1 (COX‐1) inhibition and their associated biomarkers have been proposed. A precise knowledge of endotypes will permit to discriminate patients within the same phenotype, which is crucial in order to personalise diagnosis, future treatment and prevention to improve the patient's quality of life.
Testicular cancer in 2023: Current status and recent progress
Authors: Deaglan J. McHugh, Jack P. Gleeson, Darren R. Feldman
Journal: CA A Cancer Journal for Clinicians (2023)

Abstract Testicular germ cell tumor (GCT) is the most common solid tumor in adolescent and young adult men. Progress in the management of GCT has been made in the last 50 years, with a substantial improvement in cure rates for advanced disease, from 25% in the 1970s to nearly 80%. However, relapsed or platinum‐refractory disease occurs in a proportion, 20% of whom will die from disease progression. This article reviews the current evidence‐based treatments for extracranial GCT, the acute and chronic toxic effects that may result, and highlights contemporary advances and progress in the field.
Disturbed Sleep Supports Neutrophil Activation and Promotes Atherosclerosis and Plaque Necrosis
Authors: Alina K. Moriarty, Tayab C. Waseem, W. Coles Keeter, Shelby D. Ma, Robin Bai, Aleksandr V. Ivanov, Cassandra L. Kirk, Marion Mussbacher, Larry D. Sanford, Elena V. Galkina
Journal: Circulation Research (2023)
Rapid profiling of Plasmodium parasites from genome sequences to assist malaria control
Authors: Jody E. Phelan, Anna Turkiewicz, Emilia Manko, Joseph Thorpe, Leen N. Vanheer, Marga van de Vegte-Bolmer, Nguyen Thi Hong Ngoc, Nguyen Thi Huong Binh, Nguyen Quang Thieu, Jesse Gitaka, Debbie Nolder, Khalid B. Beshir, Jamille G. Dombrowski, Silvia Maria Di Santi, Teun Bousema, Colin J. Sutherland, Susana Campino, Taane G. Clark
Journal: Genome Medicine (2023)

Abstract Background Malaria continues to be a major threat to global public health. Whole genome sequencing (WGS) of the underlying Plasmodium parasites has provided insights into the genomic epidemiology of malaria. Genome sequencing is rapidly gaining traction as a diagnostic and surveillance tool for clinical settings, where the profiling of co-infections, identification of imported malaria parasites, and detection of drug resistance are crucial for infection control and disease elimination. To support this informatically, we have developed the Malaria-Profiler tool, which rapidly (within minutes) predicts Plasmodium species, geographical source, and resistance to antimalarial drugs directly from WGS data. Results The online and command line versions of Malaria-Profiler detect ~ 250 markers from genome sequences covering Plasmodium speciation, likely geographical source, and resistance to chloroquine, sulfadoxine-pyrimethamine (SP), and other anti-malarial drugs for P. falciparum , but also providing mutations for orthologous resistance genes in other species. The predictive performance of the mutation library was assessed using 9321 clinical isolates with WGS and geographical data, with most being single-species infections ( P. falciparum 7152/7462, P. vivax 1502/1661, P. knowlesi 143/151, P. malariae 18/18, P. ovale ssp. 5/5), but co-infections were identified (456/9321; 4.8%). The accuracy of the predicted geographical profiles was high to both continental (96.1%) and regional levels (94.6%). For P. falciparum , markers were identified for resistance to chloroquine (49.2%; regional range: 24.5% to 100%), sulfadoxine (83.3%; 35.4– 90.5%), pyrimethamine (85.4%; 80.0–100%) and combined SP (77.4%). Markers associated with the partial resistance of artemisinin were found in WGS from isolates sourced from Southeast Asia (30.6%). Conclusions Malaria-Profiler is a user-friendly tool that can rapidly and accurately predict the geographical regional source and anti-malarial drug resistance profiles across large numbers of samples with WGS data. The software is flexible with modifiable bioinformatic pipelines. For example, it is possible to select the sequencing platform, display specific variants, and customise the format of outputs. With the increasing application of next-generation sequencing platforms on Plasmodium DNA, Malaria-Profiler has the potential to be integrated into point-of-care and surveillance settings, thereby assisting malaria control. Malaria-Profiler is available online (bioinformatics.lshtm.ac.uk/malaria-profiler) and as standalone software ( https://github.com/jodyphelan/malaria-profiler ).
Revolutionizing the battle against locally advanced breast cancer: A comprehensive insight into neoadjuvant radiotherapy
Authors: Xiangyi Kong, Jiarui Song, Peng Gao, Ran Gao, Lin Zhang, Yi Fang, Yipeng Wang, Jidong Gao, Jing Wang
Journal: Medicinal Research Reviews (2023)

Abstract Breast cancer (BC) constitutes one of the most pervasive malignancies affecting the female population. Despite progressive improvements in diagnostic and therapeutic technologies, leading to an increased detection of early stage BCs, locally advanced breast cancer (LABC) persists as a significant clinical challenge. Owing to its poor overall survival (OS) rate, elevated recurrence rate, and high potential for distant metastasis, LABC prominently impacts the comprehensive efficacy of BC treatments. Radiotherapy, encompassing preoperative, intraoperative, and postoperative modalities, is acknowledged as an effective strategy for mitigating BC metastasis and enhancing survival rates among patients. Nevertheless, the domain of preoperative neoadjuvant radiotherapy (NART) remains conspicuously underexplored in clinical studies. Available research suggests that NART can induce tumor volume reduction, provoke fibrotic changes in tumor and adjacent normal tissues, thereby mitigating intraoperative cancer propagation and enhancing the quality of life for LABC patients. This manuscript seeks to provide a review of contemporary research pertaining to LABC and its preoperative radiotherapy.
Stem Cells Expansion Vector via Bioadhesive Porous Microspheres for Accelerating Articular Cartilage Regeneration
Authors: Lang Bai, Qibin Han, Zeyu Han, Xiaoyu Zhang, Jingwen Zhao, Huitong Ruan, Junliang Wang, Feng Lin, Wenguo Cui, Xing Yang, Yuefeng Hao
Journal: Advanced Healthcare Materials (2023)

Abstract Stem cell tissue engineering is a potential treatment for osteoarthritis. However, the number of stem cells that can be delivered, loss of stem cells during injection, and migration ability of stem cells limit applications of traditional stem cell tissue engineering. Herein, kartogenin (KGN)‐loaded poly(lactic ‐co‐ glycolic acid) (PLGA) porous microspheres is first engineered via emulsification, and then anchored with chitosan through the amidation reaction to develop a new porous microsphere (PLGA‐CS@KGN) as a stem cell expansion vector. Following 3D co‐culture of the PLGA‐CS@KGN carrier with mesenchymal stem cells (MSCs), the delivery system is injected into the capsule cavity in situ. In vivo and in vitro experiments show that PLGA‐CS microspheres have a high cell‐carrying capacity up to 1 × 10 4 mm −3 and provide effective protection of MSCs to promote their controlled release in the osteoarthritis microenvironment. Simultaneously, KGN loaded inside the microspheres effectively cooperated with PLGA‐CS to induce MSCs to differentiate into chondrocytes. Overall, these findings indicate that PLGA‐CS@KGN microspheres held high cell‐loading ability, adapt to the migration and expansion of cells, and promote MSCs to express markers associated with cartilage repair. Thus, PLGA‐CS@KGN can be used as a potential stem cell carrier for enhancing stem cell therapy in osteoarthritis treatment.
Macrophage Membrane‐Modified MoS<sub>2</sub> Quantum Dots as a Nanodrug for Combined Multi‐Targeting of Alzheimer's Disease
Authors: Xiating Qi, Lianxin Li, Pengkun Ye, Meng Xie
Journal: Advanced Healthcare Materials (2023)

The complex pathological mechanism of Alzheimer's disease (AD) limits the efficacy of simple drug therapy, and drugs are difficult to penetrate the blood-brain barrier (BBB). Therefore, it is a breakthrough to enhance the therapeutic effect of AD by rationally using multiple therapeutic strategies to inhibit multiple pathological targets. In this study, macrophage membrane (MM) with active targeting inflammation function is used to functionalize molybdenum disulfide quantum dots (MoS
ENTERPRET: A Randomized Controlled Trial of Vedolizumab Dose Optimization in Patients With Ulcerative Colitis Who Have Early Nonresponse
Authors: Vipul Jairath, Andres Yarur, Mark T. Osterman, Alexandra James, Diane Balma, Shailly Mehrotra, Lili Yang, Vijay Yajnik, Rana M. Qasim Khan
Journal: Clinical Gastroenterology and Hepatology (2023)

BACKGROUND & AIMS Patients with ulcerative colitis (UC) may experience nonresponse to biologics, possibly due to low drug exposure. This trial assessed the efficacy of dose optimization in patients with UC who have early nonresponse to vedolizumab and high drug clearance. METHODS ENTERPRET was a phase 4, open-label, randomized controlled trial that included patients with moderate to severe UC who had high drug clearance at week 5 (serum concentration <50 μg/mL) and nonresponse to standard vedolizumab treatment at week 6. At week 6, eligible patients were randomized 1:1 to receive standard dosing (300 mg every 8 weeks) or dose-optimized vedolizumab (600 mg at week 6, then 300 mg every 4 weeks; or 600 mg at week 6, then 600 mg every 4 weeks [based on week 5 serum concentration]). The primary end point was endoscopic improvement at week 30. RESULTS Of 278 enrolled patients, 132 (47.5%) had a clinical response at week 6. From week 6, 108 patients received standard (n = 53) or dose-optimized vedolizumab (n = 55); among patients with nonresponse at week 6, 86.5% had high drug clearance. At week 30, 10 patients (18.9%) who received standard vedolizumab had endoscopic improvement versus 8 patients (14.5%) who received dose-optimized vedolizumab. Five patients (9.4%) who received standard vedolizumab had clinical remission at week 30 versus 5 patients (9.1%) who received dose-optimized vedolizumab; clinical response was observed in 17 (32.1%) and 17 patients (30.9%), respectively. Safety event rates were similar among treatment groups. CONCLUSIONS In patients with early nonresponse and high drug clearance, vedolizumab dose optimization is probably not required. A proportion of patients benefited from continued treatment irrespective of the dose received. ClinicalTrials.gov Number: NCT03029143.
News from EULAR
Journal: Annals of the Rheumatic Diseases (2023)

European Alliance of Associations for Rheumatology (EULAR) is excited to announce a new and innovative step in its mission to minimise the impact of rheumatic and musculoskeletal diseases (RMDs) on individuals and societies. EULAR focuses on creating global awareness and providing solutions for the management of RMDs through cutting-edge innovation in research, patient empowerment and expert collaboration. Read more about EULAR Strategy 2024 - 2028 %7C EULAR
Biocompatible Ferrofluid‐Based Millirobot for Tumor Photothermal Therapy in Near‐Infrared‐II Window
Authors: Yiming Ji, Xue Bai, Hongyan Sun, Luyao Wang, Chunyuan Gan, Lina Jia, Junjie Xu, Wei Zhang, Liang Wang, Yingchen Xu, Yaxin Hou, Yinyan Wang, Hui Hui, Lin Feng
Journal: Advanced Healthcare Materials (2023)

Abstract Ferrofluidic robots with excellent deformability and controllability have been intensively studied recently. However, most of these studies are in vitro and the use of ferrofluids for in vivo medicinal applications remains a big challenge. The application of ferrofluidic robots to the body requires the solution of many key problems. In this study, biocompatibility, controllability, and tumor‐killing efficacy are considered when creating a ferrofluid‐based millirobot for in vivo tumor‐targeted therapy. For biocompatibility problems, corn oil is used specifically for the ferrofluid robot. In addition, a control system is built that enables a 3D magnetic drive to be implemented in complex biological media. Using the photothermal conversion property of 1064 nm, the ferrofluid robot can kill tumor cells in vitro; inhibit tumor volume, destroy the tumor interstitium, increase tumor cell apoptosis, and inhibit tumor cell proliferation in vivo. This study provides a reference for ferrofluid‐based millirobots to achieve targeted therapies in vivo.
Kidney Outcomes and Preservation of Kidney Function With Obinutuzumab in Patients With Lupus Nephritis: A Post Hoc Analysis of the <scp>NOBILITY</scp> Trial
Authors: Brad H. Rovin, Richard A. Furie, Jorge A. Ross Terres, Sophia Giang, Thomas Schindler, Armando Turchetta, Jay P. Garg, William F. Pendergraft, Ana Malvar
Journal: Arthritis & Rheumatology (2023)

Objective To determine whether adding obinutuzumab to standard‐of‐care lupus nephritis (LN) therapy could improve the likelihood of long‐term preservation of kidney function and do so with less glucocorticoids. Methods Post hoc analyses of the phase II NOBILITY trial were performed. Time to unfavorable kidney outcome (a composite of treatment failure, doubling of serum creatinine, or death), LN flare, first 30% and 40% declines in estimated glomerular filtration rate (eGFR) from baseline, and chronic eGFR slope during the trial were compared between patients with active LN who were randomized to take obinutuzumab (n = 63) or placebo (n = 62) in combination with mycophenolate mofetil and glucocorticoids. The number of patients who achieved complete renal response (CRR) on 7.5 mg or less per day of prednisone was also determined. Results Obinutuzumab reduced the risk of developing the composite kidney outcome by 60%, LN flare by 57%, and first eGFR decline of 30% or 40% by 80% and 91%, respectively. Patients receiving obinutuzumab had a significantly slower decline in eGFR than patients receiving placebo, with an annualized eGFR slope advantage of 4.1 ml/min/1.73 m 2 /year (95% confidence interval 0.14–8.08). Overall, 38% of patients receiving obinutuzumab compared with 16% of patients receiving placebo achieved CRR at week 76 while receiving 7.5 mg or less per day of prednisone ( P &lt; 0.01); at week 104, the difference did not achieve significance (38% vs 22%; P = 0.06). Conclusion Post hoc analyses of NOBILITY demonstrated that compared with standard‐of‐care therapy, obinutuzumab treatment resulted in superior preservation of kidney function and prevention of LN flares. More patients achieved CRR at week 76 with less glucocorticoid use in the obinutuzumab group. image
Pathophysiology to advanced intra-articular drug delivery strategies: Unravelling rheumatoid arthritis
Authors: Hemant Singh, Aniruddha Dan, Mukesh Kumar Kumawat, Vaishali Pawar, Deepak S. Chauhan, Ajeet Kaushik, Dhiraj Bhatia, Rohit Srivastava, Mukesh Dhanka
Journal: Biomaterials (2023)
The circadian clock time tunes axonal regeneration
Authors: Francesco De Virgiliis, Franziska Mueller, Ilaria Palmisano, Jessica Sarah Chadwick, Lucia Luengo-Gutierrez, Angela Giarrizzo, Yuyang Yan, Matt Christopher Danzi, Carmen Picon-Muñoz, Luming Zhou, Guiping Kong, Elisabeth Serger, Thomas Haynes Hutson, Ines Maldonado-Lasuncion, Yayue Song, Christoph Scheiermann, Marco Brancaccio, Simone Di Giovanni
Journal: Cell Metabolism (2023)
Efficacy of sequential chemoradiotherapy combined with toripalimab in de novo metastatic nasopharyngeal carcinoma: A phase II trial
Authors: Si-Yuan Chen, Xiao-Tong Duan, Hui-Feng Li, Lan Peng, Zhi-Qiang Wang, Gui-Qiong Xu, Yi-Jun Hua, Xiong Zou, Rui You, Yan-Feng Ouyang, You-Ping Liu, Chen-Mei Gu, Qi Yang, Rou Jiang, Meng-Xia Zhang, Mei Lin, Yu-Long Xie, Chao Lin, Xi Ding, Ruo-Qi Xie, Chong-Yang Duan, Wei-Jing Zhang, Pei-Yu Huang, Ming-Yuan Chen
Journal: Cell Reports Medicine (2023)

Locoregional radiotherapy added to chemotherapy has significantly improved survival in de novo metastatic nasopharyngeal carcinoma (mNPC). However, only 54% of de novo mNPC patients who received sequential chemoradiotherapy have complete or partial response 3 months after radiotherapy. This Simon's optimal two-stage design phase II study (NCT04398056) investigates whether PD-1 inhibitor could improve tumor control in combination with chemoradiation. The primary endpoint is objective response rate (ORR) at 3 months after radiotherapy. Twenty-two patients with primary mNPC are enrolled. The ORR at 3 months after radiotherapy is 81.8% (22.7% complete response, n = 5; 59.1% partial response, n = 13), and the disease control rate is 81.8%. The 3-year progression-free survival (PFS) rate is 44.9% (95% confidence interval 26.4%–76.3%). Fifteen patients (68.2%) experienced grade 3–4 adverse events. Patients with high baseline plasma Epstein-Barr virus DNA copy number (>104 cps/mL) show worse PFS. Addition of toripalimab to sequential chemoradiotherapy suggests promising tumor response in patients with primary mNPC.